HSS Journal

, 5:149

Recent Advances Toward the Clinical Application of PTH (1-34) in Fracture Healing

  • Cara A. Cipriano
  • Paul S. Issack
  • Lisa Shindle
  • Clément M. L. Werner
  • David L. Helfet
  • Joseph M. Lane


PTH 1-34, an active form of parathyroid hormone, has been shown to enhance osteoblastic bone formation when administered as a daily subcutaneous injection. The effect of the intermittent administration of PTH (1-34) is an uncoupling of bone turnover with an increase in bone mass and density and decrease in risk of vertebral and nonvertebral fractures. While PTH (1-34) has been used clinically to increase bone mass and reduce fracture risk in postmenopausal women with osteoporosis, there is increasing evidence that PTH (1-34) may promote fracture healing. Animal studies have demonstrated accelerated callus formation with enhanced remodeling and biomechanical properties of the healing fracture. Given these effects, PTH (1-34) will likely be used clinically to enhance fracture union in poor healing situations such as osteoporosis and recalcitrant nonunions.


  1. 1.
    Madore GR, Sherman PJ, Lane JM (2004) Parathyroid hormone. J Am Acad Orthop Surg 12:67–71PubMedGoogle Scholar
  2. 2.
    Finkelstein JS, Hayes A, Hunzelman JL et al (2003) The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 349:1216–1226PubMedCrossRefGoogle Scholar
  3. 3.
    Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRefGoogle Scholar
  4. 4.
    Alkhiary YM, Gerstenfeld LC, Krall E et al (2005) Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). J Bone Joint Surg Am 87:731–741PubMedCrossRefGoogle Scholar
  5. 5.
    Andreassen TT, Ejersted C, Oxlund H (1999) Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures. J Bone Miner Res 14:960–968PubMedCrossRefGoogle Scholar
  6. 6.
    Andreassen TT, Fledelius C, Ejersted C et al (2001) Increases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone. Acta Orthop Scand 72:304–307PubMedCrossRefGoogle Scholar
  7. 7.
    Andreassen TT, Willick GE, Morley P et al (2004) Treatment with parathyroid hormone hPTH(1-34), hPTH(1-31), and monocyclic hPTH(1-31) enhances fracture strength and callus amount after withdrawal fracture strength and callus mechanical quality continue to increase. Calcif Tissue Int 74:351–356PubMedCrossRefGoogle Scholar
  8. 8.
    Holzer G, Majeska RJ, Lundy MW et al (1999) Parathyroid hormone enhances fracture healing. A preliminary report. Clin Orthop Relat Res 366:258–263PubMedCrossRefGoogle Scholar
  9. 9.
    Jahng JS, Kim HW (2000) Effect of intermittent administration of parathyroid hormone on fracture healing in ovariectomized rats. Orthopedics 23:1089–1094PubMedGoogle Scholar
  10. 10.
    Komatsubara S, Mori S, Mashiba T et al (2005) Human parathyroid hormone (1-34) accelerates the fracture healing process of woven to lamellar bone replacement and new cortical shell formation in rat femora. Bone 36:678–687PubMedCrossRefGoogle Scholar
  11. 11.
    Nakajima A, Shimoji N, Shiomi K et al (2002) Mechanisms for the enhancement of fracture healing in rats treated with intermittent low-dose human parathyroid hormone (1-34). J Bone Miner Res 17:2038–2047PubMedCrossRefGoogle Scholar
  12. 12.
    Nakazawa T, Nakajima A, Shiomi K et al (2005) Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1-34) on chondrogenesis in a model of experimental fracture healing. Bone 37:711–719PubMedCrossRefGoogle Scholar
  13. 13.
    Kronenberg HM (2006) PTHrP and skeletal development. Ann N Y Acad Sci 1068:1–13PubMedCrossRefGoogle Scholar
  14. 14.
    Martin TJ, Quinn JM, Gillespie MT et al (2006) Mechanisms involved in skeletal anabolic therapies. Ann N Y Acad Sci 1068:458–470PubMedCrossRefGoogle Scholar
  15. 15.
    Everhart-Caye M, Inzucchi SE, Guinness-Henry J et al (1996) Parathyroid hormone (PTH)-related protein(1-36) is equipotent to PTH(1-34) in humans. J Clin Endocrinol Metab 81:199–208PubMedCrossRefGoogle Scholar
  16. 16.
    Hock JM, Fonseca J, Gunness-Hey M et al (1989) Comparison of the anabolic effects of synthetic parathyroid hormone-related protein (PTHrP) 1-34 and PTH 1-34 on bone in rats. Endocrinology 125:2022–2027PubMedCrossRefGoogle Scholar
  17. 17.
    Weir EC, Terwilliger G, Sartori L et al (1992) Synthetic parathyroid hormone-like protein (1-74) is anabolic for bone in vivo. Calcif Tissue Int 51:30–34PubMedCrossRefGoogle Scholar
  18. 18.
    Okazaki K, Jingushi S, Ikenoue T et al (2003) Expression of parathyroid hormone-related peptide and insulin-like growth factor I during rat fracture healing. J Orthop Res 21:511–520PubMedCrossRefGoogle Scholar
  19. 19.
    Chung UI, Lanske B, Lee K et al (1998) The parathyroid hormone/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation. Proc Natl Acad Sci U S A 95:13030–13035PubMedCrossRefGoogle Scholar
  20. 20.
    Kobayashi T, Chung UI, Schipani E et al (2002) PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Development 129:2977–2986PubMedGoogle Scholar
  21. 21.
    Lanske B, Karaplis AC, Lee K et al (1996) PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science 273:663–666PubMedCrossRefGoogle Scholar
  22. 22.
    Vortkamp A, Lee K, Lanske B et al (1996) Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273:613–622PubMedCrossRefGoogle Scholar
  23. 23.
    Dempster DW, Cosman F, Kurland ES et al (2001) Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res 16:1846–1853PubMedCrossRefGoogle Scholar
  24. 24.
    Lindsay R, Zhou H, Cosman F et al (2007) Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res 22:495–502PubMedCrossRefGoogle Scholar
  25. 25.
    Misof BM, Roschger P, Cosman F et al (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88:1150–1156PubMedCrossRefGoogle Scholar
  26. 26.
    Bostrom MP, Gamradt SC, Asnis P et al (2000) Parathyroid hormone-related protein analog RS-66271 is an effective therapy for impaired bone healing in rabbits on corticosteroid therapy. Bone 26:437–442PubMedCrossRefGoogle Scholar
  27. 27.
    Miller PD, Schwartz EN, Chen P et al (2007) Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int 18:59–68PubMedCrossRefGoogle Scholar
  28. 28.
    Miller PD, Bilezikian JP, Diaz-Curiel M et al (2007) Occurrence of hypercalciuria in patients with osteoporosis treated with teriparatide. J Clin Endocrinol Metab 92(9):3535–3541PubMedCrossRefGoogle Scholar
  29. 29.
    Medication Guide. Indianapolis I Eli Lilly and Company 2002Google Scholar
  30. 30.
    Vahle JL, Sato M, Long GG et al (2002) Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. Toxicol Pathol 30:312–321PubMedCrossRefGoogle Scholar
  31. 31.
    Vahle JL, Zuehlke U, Schmidt A et al (2008) Lack of bone neoplasms and persistence of bone efficacy in cynomolgus macaques after long-term treatment with teriparatide [rhPTH(1-34)]. J Bone Miner Res 18:9–17Google Scholar

Copyright information

© Hospital for Special Surgery 2009

Authors and Affiliations

  • Cara A. Cipriano
    • 3
  • Paul S. Issack
    • 1
    • 2
  • Lisa Shindle
    • 4
  • Clément M. L. Werner
    • 1
  • David L. Helfet
    • 1
    • 5
  • Joseph M. Lane
    • 4
  1. 1.Orthopaedic Trauma ServiceHospital for Special SurgeryNew YorkUSA
  2. 2.Orthopaedic Trauma and Adult Reconstructive SurgeryHospital for Special SurgeryNew YorkUSA
  3. 3.University of Pennsylvania School of MedicinePhiladelphiaUSA
  4. 4.Metabolic Bone Disease ServiceHospital for Special SurgeryNew YorkUSA
  5. 5.Weill-Cornell Medical CenterNew YorkUSA

Personalised recommendations